Project Summary. Although the frequency of comorbidity is a well-established aspect of adolescent psychopathology, little is known regarding the effective delivery of treatment services to youth with comorbid conditions. In an effort to improve treatment engagement, response, and maintenance of gains, the proposed study will evaluate service delivery methods of integrating two empirically-supported interventions, the Adolescent Coping With Depression course (ACWD) and Functional Family Therapy (FFT), for depressive disorder and substance use disorders (SLID), respectively. Over a 5-year period, 180 adolescents (ages 13-17) from Portland, OR and Albuquerque, NM diagnosed with depression and SUD, and their parents/guardians will be recruited and randomly assigned to one of three treatment delivery conditions: (a) FFT followed by ACWD, (b) ACWD followed by FFT, or (c) an integrated intervention combining and augmenting the ACWD and FFT interventions. Treatment in each condition will consist of 24 (12 families and 12 groups) sessions provided over a 20 week period. Participants will be assessed at intake, after 6,12, 18, and 24 treatment sessions (i.e., Post-Treatment), and at 3-, 6-, and 9-month follow-up. By providing ACWD and FFT interventions in both sequences, we will evaluate whether depression maintains SUD (Self-Medication model), SUD maintains depression (Affective Consequences model), each disorder maintains the other (Reciprocal Relations model), or both are maintained by other variables (Independent Factors model). In addition, integrating interventions to target both disorders in a coordinated fashion is expected to enhance the efficacy of treatment for youth with co-occurring disorders compared to a sequence of treatment that targets only one disorder at a time. Moreover, because the integrated treatment will address both conditions in early sessions, higher engagement rates are expected, compared to either sequenced treatment delivery. The study will also examine whether depressotypic cognitions and pleasant activities mediate the effects of ACWD and if improved family functioning mediates the effects of FFT. Relative severity or temporal onset of the two disorders will be examined as potential moderators of treatment outcome. Relevance. The co-occurrence of depression and SUD exacerbates problems in functioning and increases distress (e.g., elevated rates of suicide attempts and completion). Comorbidity also complicates the selection and delivery of treatment services and is generally associated with higher drop-out and lower treatment response. The proposed project represents the first study to experimentally evaluate interventions for adolescents with co-occurring depression and substance use disorders. Testing the combination and sequencing of empirically supported treatments will provide critical information regarding the influence of each disorder on the other and yield important information regarding how to most effectively provide treatment services in a clinically meaningful and data-driven manner.